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目的评价单倍体造血干细胞移植对假肥大型肌营养不良症(DMD)缺失基因替代、抗肌萎缩蛋白表达和运动功能的变化。方法经解放军第463医院伦理委员会批准,患者家属签署知情同意书,于2010年4月应用单倍体造血干细胞移植术治疗1例8岁男性DMD患儿。多重连接酶依赖探针扩增方法(MLPA)基因分析13外显子缺失。观察血清酶学变化、供者HLA植入证据、缺陷基因表达、肌细胞膜抗肌萎缩蛋白表达、运动功能改善情况。结果造血干细胞移植后15 d(+15 d)造血功能恢复正常;+15 d、+30 d、+60 d患儿骨髓、外周血检测聚合酶链反应-短串联重复序列(PCR-STR)均为完全供者型嵌合;+15 d MLPA检测缺失的13外显子得到纠正,为正常基因表达;+85 d肌肉活检示为供受者嵌和状态(11.23%),缺失的13外显子弱阳性表达。肌细胞形态改善,抗肌萎缩蛋白间断弱阳性表达;血清肌酸激酶(CK)、肌酸激酶同工酶(CK-BM)、乳酸脱氢酶(LDH)显著降低;肌电图波幅及波形较移植前改善;移植术后肌力提高0.5～1.0级,运动功能明显改善,ADL评分较治疗前显著增加。结论单倍体造血干细胞移植术治疗DMD可使缺失基因替代,肌细胞膜抗肌萎缩蛋白阳性表达,血清酶学显著降低,提高运动功能。可阻止DMD患儿疾病进展,有望获得持续性改善。
Objective To evaluate the changes of gene replacement, dystrophin expression and motor function of haploidentical hematopoietic stem cell transplantation in patients with duodenal dystrophy (DMD). Methods Approved by the People’s Liberation Army 463 Hospital Ethics Committee, the patients’ relatives signed the informed consent, and in April 2010 a hapten hematopoietic stem cell transplantation was used to treat 1 8-year-old male with DMD. Multiplexase Dependent Probe Amplification Method (MLPA) Gene Analysis 13 Exon Deletion. Serum enzyme changes, evidence of donor HLA implantation, defective gene expression, muscle dystrophin expression, and motor function were observed. Results The hematopoietic function returned to normal after 15 days (+15 days) of hematopoietic stem cell transplantation. The levels of PCR-STR and PCR-STR in bone marrow and peripheral blood of +15 days, +30 days and +60 days Was completely donor-type chimeric. The deletion of exon 13 by MLPA was corrected for normal gene expression at +15 days. The muscle biopsy at +85 d showed donor imbedding (11.23%), deletion of 13 Weak positive expression. Muscle cell morphology was improved and dystrophin expression was weakly weakly positive. Serum creatine kinase (CK), creatine kinase (CK-BM) and lactate dehydrogenase (LDH) Compared with pretransplantation, the improvement of muscle strength was 0.5 ~ 1.0 after exercise and the motor function was improved obviously. The ADL score increased significantly compared with that before treatment. Conclusion The haploidentical hematopoietic stem cell transplantation for the treatment of DMD can replace the deletion gene, muscle dystrophin protein positive expression, serum enzyme was significantly reduced, improve motor function. Can prevent disease progression in children with DMD, is expected to be sustained improvement.